Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial

The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies

“…The SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies were randomized, double-blind, parallel-group, placebo-controlled, Phase III studies that enrolled patients at 303 and 374 clinical research centers, respectively, in Africa, Asia, Europe, North America, and South America 20,21 . The study design comprised an enrollment visit (Week -4), a 4-week screening/run-in phase, randomization (Week 0), a treatment period from Weeks 0 to 48 (SIROCCO) or 56 (CALIMA), and a final follow-up visit 4 weeks following the end of the treatment period.…”

“…Enrollment criteria for the studies have been published 20,21 . The study included male and female patients aged 12-75 years, with a weight of !40 kg, and with physician-diagnosed asthma that required treatment with medium-to high-dosage ICS/LABA (defined as fluticasone !500 lg/day or equivalent total daily dosage) for !12 months prior to enrollment.…”

“…Because there was no apparent safety or efficacy benefit to more frequent benralizumab dosing in either the SIROCCO or CALIMA studies, only benralizumab 30 mg Q8W was explored further in the current analysis 20,21 . The Q8W regimen has indicated greater numerical trends (statistical tests not evaluated) toward efficacy benefits, and a smaller drug burden compared with the Q4W regimen 20,21 .…”

“…In contrast, the Phase III benralizumab trials included patients irrespective of blood eosinophil count, so it was possible to assess efficacy across a range of blood eosinophils. Of note, benralizumab demonstrated efficacy for patients with a screening blood eosinophil count <300 cells/lL 20,21 . The aim of the current study was to further characterize the patient population most likely to benefit from benralizumab treatment.…”

“…In this respect, benralizumab differs from the two marketed anti-IL-5 antibodies (mepolizumab and reslizumab) that bind IL-5 and result in passive, indirect eosinophil reduction [17][18][19] . In two Phase III studies, SIROCCO and CALIMA, adding subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; Q4W for the first three doses) to ICS/LABA significantly reduced asthma exacerbations, increased lung function (forced expiratory volume in 1 s [FEV 1 ]), improved symptom control, and depleted blood eosinophils for patients with severe, uncontrolled asthma and a screening blood eosinophil count of !300 cells/lL 20,21 . Both benralizumab dosing regimens reduced the frequency of exacerbations relative to that with placebo for patients with blood eosinophil counts <300 cells/lL in CALIMA and with the benralizumab Q4W regimen in SIROCCO 20,21 .…”